Immunocompetent T-Cells with a Memory-Like Phenotype are the Dominant Cell Type Following Antibody-Mediated T-Cell Depletion

Authors

  • Jonathan P. Pearl,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Surgery, National Naval Medical Center, Bethesda, Maryland, USA
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  • Jeremy Parris,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Douglas A. Hale,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Organ Transplant Service, Walter Reed Army Medical Center, Washington, District of Columbia, USA
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  • Steven C. Hoffmann,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Wendy B. Bernstein,

    1. Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland, USA
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  • Kelly L. McCoy,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Surgery, National Naval Medical Center, Bethesda, Maryland, USA
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  • S. John Swanson,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Organ Transplant Service, Walter Reed Army Medical Center, Washington, District of Columbia, USA
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  • Roslyn B. Mannon,

    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Surgery, National Naval Medical Center, Bethesda, Maryland, USA
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  • Mario Roederer,

    1. Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Allan D. Kirk

    Corresponding author
    1. Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Surgery, National Naval Medical Center, Bethesda, Maryland, USA
    3. Organ Transplant Service, Walter Reed Army Medical Center, Washington, District of Columbia, USA
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*Corresponding author: Allan D. Kirk, AllanK@intra.niddk.nih.gov

Abstract

T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naïve T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain immunosuppressants, but cannot be considered uniquely pro-tolerant.

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